PDLLA and PLGA are biodegradable and biocompatible polymers which have been extensively used for various biomedical applications for a long time, especially for drug and vaccine delivery. Polymer particle based vaccine delivery systems provide a viable alternative to multi-dose immunization schedule for many infectious diseases where neutralizing antibody titers provide protective immunity. Particles, particularly made from poly lactide-co-glycolide (PLGA) or PLA, not only work as a delivery system but also provide adjuvant activity.
These polymeric particulate delivery systems have the capacity to promote presentation of the antigen by both MHC class I (MHC I) and MHC class II (MHC II) pathway and thus can activate both humoral and cellular response. Efficient targeting of particulate antigen to the APCs has been reported as a major factor contributing towards the generation of immune response, which requires that the particle size should be between 1-10 μm. The improved immunogenicity of polymer particle entrapped antigen is associated with the continuous delivery of the antigen in to APC and its interaction with macrophages, DC etc for antigen presentation. Immunogenicity of many antigens has been improved while entrapping them in different sized PLA/PLGA particles. However there are no reports on the improved immunogenicity of T independent antigen using PLGA/PLA based polymer particle formulation.
One of the major problems associated with T independent candidate vaccine is the poor generation of memory antibody response after immunization. Memory antibody response is the hall mark of immunity and in absence of it the vaccine has little or no value. To elicit memory antibody, T independent antigens (mostly carbohydrates) are conjugated to a T helper epitope. Conjugation is costly and introduces another candidate antigen to the system. It will be ideal if the memory antibody to carbohydrates antigen can be elicited without conjugation to any other antigenic determinants. In such scenario, entrapments of the carbohydrate antigen in polymer particle alone or in combination of another T helper epitope provide a viable alternative to conjugate.
The innovation described in the patents aims towards the development of carbohydrate vaccine formulation having capacity to elicit memory antibody response. Vi polysaccharide of Salmonella typhi is entrapped in polymer particles of desired size and immunized without any adjuvant. Single point immunization of polymer particle entrapped Vi polysaccharide elicit both primary and memory antibody titers in experiments animals.